Separate classes of inhibitory neurons target proximal and distal regions at pyramidal cells and thus impact differentially the processing of visual information in the cortex. However, the mechanisms that allow selective activation of specific classes of inhibitory neurons are unknown. In this proposal we will study the pre- and postsynaptic mechanisms activating specific classes of inhibitory neurons. We will test the hypothesis that inhibitory neurons targeting proximal vs. distal pyramidal cell regions differ in the temporal integration of their excitatory inputs. More specifically, we will test the proposal that spike timing is important at proximally targeting fast-spiking (FS) cells, whereas late-spiking (LS) and low threshold spiking (LTS) cells, inhibiting distal dendrites, integrate their excitatory inputs over a prolonged period of time. The specific aims are: Specific Aim 1: We will compare the functional properties of AMPA and NMDA receptors mediating EPSPs at FS inhibitory neurons, targeting the soma and proximal dendrites of pyramidal cells, and at LS and LTS cells, targeting distal dendrites. Specific Aim 2: We will compare how postsynaptic voltage-dependent mechanisms determine the way different patterns of EPSPs are integrated and produce action potentials at proximally targeting FS cell and at distally targeting LS and LTS GABAergic interneuron. Specific Aim 3: We will study the developmental and experience-dependent regulation of excitatory synapses in proximally and distally targeting GABAergic interneurons.